Cell Host Microbe . Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses

[tetano]

Cell Host Microbe


. 2022 Nov 4;S1931-3128(22)00523-6.
doi: 10.1016/j.chom.2022.10.010. Online ahead of print.
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses


Cherrelle Dacon ¹ , Linghang Peng ² , Ting-Hui Lin ³ , Courtney Tucker ⁴ , Chang-Chun D Lee ³ , Yu Cong ⁵ , Lingshu Wang ⁶ , Lauren Purser ¹ , Andrew J R Cooper ¹ , Jazmean K Williams ⁷ , Chul-Woo Pyo ⁸ , Meng Yuan ³ , Ivan Kosik ⁹ , Zhe Hu ⁹ , Ming Zhao ¹⁰ , Divya Mohan ¹ , Mary Peterson ¹¹ , Jeff Skinner ¹¹ , Saurabh Dixit ⁵ , Erin Kollins ⁵ , Louis Huzella ⁵ , Donna Perry ⁵ , Russell Byrum ⁵ , Sanae Lembirik ⁵ , Michael Murphy ⁵ , Yi Zhang ⁶ , Eun Sung Yang ⁶ , Man Chen ⁶ , Kwanyee Leung ⁶ , Rona S Weinberg ¹² , Amarendra Pegu ⁶ , Daniel E Geraghty ⁸ , Edgar Davidson ⁷ , Benjamin J Doranz ⁷ , Iyadh Douagi ¹³ , Susan Moir ¹⁴ , Jonathan W Yewdell ⁹ , Connie Schmaljohn ⁵ , Peter D Crompton ¹¹ , John R Mascola ⁶ , Michael R Holbrook ⁵ , David Nemazee ² , Ian A Wilson ¹⁵ , Joshua Tan ¹⁶



Affiliations

• PMID: 36347257
• DOI: 10.1016/j.chom.2022.10.010

Abstract

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; betacoronavirus; broadly neutralizing antibodies; monoclonal antibody; stem helix; variants of concern.